Phase Ib study of talimogene laherparepvec (T-VEC) in combination with chemotherapy (CT) or endocrine therapy (ET) in patients with metastatic, unresectable, or locoregionally recurrent HER2-negative breast cancer (BC).
Authors: Laura Ann Huppert, Amelia S Gliwa, Madeline Tait, Laura Quintal, Stephanie Starzinski, Alexander Cheung, Mark M. Moasser, Melanie Majure, Michelle E. Melisko, Hope S. Rugo, Pamela N. Munster, Michael J. Campbell, Lawrence Fong, Amy Jo Chien
Journal: Journal of Clinical Oncology (2023)

1091 Background: Talimogene laherparepvec (TVEC) is a modified oncolytic herpes simplex 1 (HSV1) virus that may enhance tumor immune infiltration and is currently FDA-approved for the treatment of unresectable cutaneous, subcutaneous, and nodal melanoma. Anti-tumor responses have been seen both locally and systemically, and an abscopal systemic effect has been described in distant organ metastases. Methods: In this single arm, open label Phase 1b study, patients received intra-tumoral TVEC (first dose 10 6 PFU/mL followed by 10 8 PFU/mL q2-3 weeks; volume based on tumor size up to max 4mL) in combination with CT (gemcitabine/carboplatin [GC], nab-paclitaxel [Nab-P], or paclitaxel [P]) or ET at the discretion of the treating physician. All patients had at least one 1 cm lesion that was injectable at the bedside. The primary endpoint was safety and tolerability. The secondary endpoint was response by RECIST 1.1. Blood and tissue-based immune correlates including injected and neighboring non-injected lesions were evaluated. Results: 19 pts were enrolled on this study (2/5/20 – 1/25/23) and evaluable for toxicity with 1 pt non-evaluable for efficacy due to early discontinuation. Median age was 52.1 years. Nine pts (47%) had HR+/HER2- BC and 10 pts (53%) had TNBC. Injected lesions included intact subcutaneous skin nodules (7), non-fungating breast or chest wall lesions (12), and fungating breast or chest wall lesions (9). Pts had a median of 3 prior lines of systemic therapy in the metastatic setting (range 0-9). 13 pts (74%) had visceral metastases. Pts received TVEC with the following treatment partners: GC (n=8, 42%), Nab-P (n=7, 37%), P (n=2, 11%), ET (n=2, 10%). Median treatment duration was 11.6 weeks (range 1.0-45.0 weeks). Grade 3-4 treatment-related adverse events included neutropenia (n=5, 26%), anemia (n=1, 5%), thrombocytopenia (n=1, 5%), and injection site skin ulceration (n=1, 5%). Three pts (16%) had Grade 1-2 injection site skin ulceration. Response per RECIST 1.1 was evaluated in 16 pts (2 pts had rapid progression prior to first response evaluation): PR (n=2, 13%), SD (n=5, 31%), and PD (n=9, 56%). Disease response at the site of TVEC injection was clinically evaluated in 18 pts, with response rates (RR) as follows: partial response (PR) (n=11, 61%), stable disease (SD) (n=4, 22%), and progressive disease (PD) (n=3, 17%). Mass cytometry (CyTOF) analysis demonstrated a decrease in HLA-DR expression circulating lymphocytes and in TIM3 expression across multiple cell types in responders vs. non-responders; updated correlative analyses will be presented. Conclusions: The addition of intra-tumoral TVEC to CT or ET is safe and tolerable in pts with advanced BC. This treatment induces changes in circulating immune responses. Clinical trial information: NCT03554044 .